15 research outputs found

    Changes in chromatin structure during processing of wax-embedded tissue sections

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    The use of immunofluorescence (IF) and fluorescence in situ hybridisation (FISH) underpins much of our understanding of how chromatin is organised in the nucleus. However, there has only recently been an appreciation that these types of study need to move away from cells grown in culture and towards an investigation of nuclear organisation in cells in situ in their normal tissue architecture. Such analyses, however, especially of archival clinical samples, often requires use of formalin-fixed paraffin wax-embedded tissue sections which need addition steps of processing prior to IF or FISH. Here we quantify the changes in nuclear and chromatin structure that may be caused by these additional processing steps. Treatments, especially the microwaving to reverse fixation, do significantly alter nuclear architecture and chromatin texture, and these must be considered when inferring the original organisation of the nucleus from data collected from wax-embedded tissue sections

    Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

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    Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

    Guidelines for licensing CO2 storage operations around the globe

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    In January 2008, the European Commission proposed a directive on the geologic storage of CO2 in the EU. Simultaneous to the development of the directive by the EC, the CO2 ReMoVe project, funded by FP6 and industry, wrote a draft contribution to future guidelines for licensing of CO2 storage in saline reservoirs and depleted hydrocarbon reservoirs. This document contains detailed checklists for operators and authorities in each of the stages of a licensing procedure for a CO2 storage operation. The draft guidelines will be updated as results from monitoring ongoing CO2 storage operations become available. They may serve as a contribution to the regulation of CO2 storage anywhere in the world, and may be also be of use in evaluating the EU directive in the futur

    Scoring Multipole Electrostatics in Condensed-Phase Atomistic Simulations

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    Permanent multipoles (MTPs) embody a natural extension to common point-charge (PC) representations in atomistic simulations. In this work, we propose an alternative to the computationally expensive MTP molecular dynamics simulations by running a simple PC simulation and later reevaluate—“score’’—all energies using the more detailed MTP force field. The method, which relies on the assumption that the PC and MTP force fields generate closely related phase spaces, is accomplished by enforcing identical sets of monopoles between the two force fields—effectively highlighting the higher MTP terms as a correction to the PC approximation. We first detail our consistent parametrization of the electrostatics and van der Waals interactions for the two force fields. We then validate the method by comparing the accuracy of protein–ligand binding free energies from both PC and MTP-scored representations with experimentally determined binding constants obtained by us. Specifically, we study the binding of several arylsulfonamide ligands to human carbonic anhydrase II. We find that both representations yield an accuracy of 1 kcal/mol with respect to experiment. Finally, we apply the method to rank the energetic contributions of individual atomic MTP coefficients for molecules solvated in water. All in all, MTP scoring is a computationally appealing method that can provide insight into the multipolar electrostatic interactions of condensed-phase systems

    Polycomb and trithorax opposition in development and disease

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